The sting injury by the jellyfish in sea bathing has occurred in various parts of the world. The sting injury by Carybdea rastonii or Physalia physalis has also occurred frequently in Japan every year in the season of sea bathing of the summertime. The degree of the symptom by sting differs by species of a jellyfish and the individual differences of patients. The first symptom is dermotoses, such as pain, flare, papule, vesicle and so on in the sting site. In a serious illness, patients may die with generating of hemorrhagic maculae and the necrosis, and also constitutional symptom, such as headache, high fever, nausea, dyspnea, and the fluctuation of a pulse. Although such sting injury is occurring frequently, the determination and pharmacological properties of the toxic components of jellyfish have not been studied intensively. Therefore, the development of medicines for treatment of the sting by the jellyfish is hardly performed before the present invention.
For example, the serious sting injury by Carybdea alata in Hawaii or other places has been reported (R. H. Tamanaha et al., J. Am. Acad. Dermatol., 1996, 35, 991-993); however, the determination and pharmacological properties of the toxic components of this jellyfish have not been studied. On the contrary, the studies on the toxic components of Carybdea rastonii, which is family relation to Carybdea alata, have been well studied, and chemical and physiological properties of the toxic component of Carybdea rastonii have been clarified (Akihiko Sato, “Research on the toxic component of Carybdea rastonii”, The Journal of the Ochanomizu Medico-dental Society, vol. 33, No. 2, 131-151, June 1985; International Laid-open Patent Publication No. WO99/50294).
On the one hand, since the known poisons from the nematocyst of a jellyfish were non-dialyzable high polymer and deactivated by treatment with acid or alkali, or by heating processing, organic solvent processing, protease processing, etc., it was thought that the main components of poison were proteins.
Moreover, the purification of the protein toxin derived from a jellyfish has also been tried; however, the isolation and the purification of the active components maintaining the hemolytic activity were not performed since the toxin of a jellyfish itself was very easy to be deactivated. Therefore, the physical and chemical properties of the toxin from jellyfish have never been clarified up to now. However, the method for isolation and purification of the unstable toxic components of jellyfish in good yields has been reported recently in the International Laid-open Patent Publication No. WO99/50294.
The detailed studies on the toxic component of a jellyfish is very important for the development of drugs applying their various physiological activities, in particular, specific hemolytic activity and the cytotoxic effect, and for the development of medicines for treatment of the sting injury by the jellyfish.
Therefore, the problems to be solved by the present invention is providing an approach to development of the drugs for treatment of the sting injury by the jellyfish by means of isolating the proteins or peptides having as potent hemolytic activity as possible, in the state where the physiologic activity is retained. The present invention further provides the approach to study similarities on embryology or structure, and the species specificity of the protein having hemolytic activity to evaluate the structure-activity relationship thereof.